Liver toxicity and carcinogenicity in F344/N rats and B6C3F1 mice exposed to Kava Kava

Abstract

Kava Kava is an herbal supplement used as an alternative to antianxiety drugs. Although some reports suggest an association of Kava Kava with hepatotoxicity , it continues to be used in the United States due to lack of toxicity characterization. In these studies F344/N rats and B6C3F1 mice were administered Kava Kava extract orally by gavage in corn oil for two weeks, thirteen weeks or two years. Results from prechronic studies administered Kava Kava at 0.125- to 2g/kg body weight revealed dose-related increases in liver weights and incidences of hepatocellular hypertrophy. In the chronic studies, there were dose-related increases in the incidences of hepatocellular hypertrophy in rats and mice administered Kava Kava for up to 1 g/kg body weight. This was accompanied by significant increases in incidences of centrilobular fatty change. There was no treatment- related increase in carcinogenic activity in the livers of male or female rats in the chronic studies. Male mice showed a significant dose-related increase in the incidence of hepatoblastomas. In female mice, there was a significant increase in the combined incidence of hepatocellular adenoma and carcinoma in the low and mid dose groups but not in the high dose group. These findings were accompanied by several nonneoplastic hepatic lesions.

Effect of quercetin against lindane induced alterations in the serum and hepatic tissue lipids in wistar rats

“…The liver is a metabolically versatile organ responsible for the regulation of internal chemical environment [36] . It is particularly important in the synthesis and regulation of circulating lipids, lipoproteins, triglycerides, cholesterol, cholesterol esters and in the degradation of cholesterol and steroids.…”

Subchronic and Chronic Toxicities of African Medicinal Plants

“…Subchronic studies following oral exposure to Kavain (10À400 mg/kg) in dogs for 91 days revealed the presence of mild toxicity with multicentric liver necrosis in a high dose dog [50]. Similarly, subchronic and chronic toxicity studies of 1 and 2 g/kg of Kava Kava in rats and mice reported for 3 months and 2 years, respectively, was associated with weight loss, ataxia and lethargy, hepatomegaly, and varying degrees of hepatotoxicity and hepatic cholestasis in both sexes of the animal species used [51]. Similarly, in humans, the main concern with the use of Kava Kava is hepatotoxicity in humans [52À56].…”

Carcinogenic herbs: a review

“…Centrilobular hypertrophy was also observed which was portrayed by enlargement of centrilobular hepatocytes with raised amounts of eosinophilic cytoplasm and enlarged nuclei. [15] So from above studies it is clear that Kava kava has the potential to induce liver cancers and may affect pancreas too, so it should be consumed carefully.…”